1. Field of the Invention
The invention relates to a method for analyzing irreversible apneic coma (IAC), and in particular, a method for analyzing irreversible apneic coma (IAC) based on the analysis of heart rate variability (HRV) by means of Poincaré plot.
2. Description of the Prior Art
In an intensive care unit, a patient with irreversible apneic coma (IAC) has a great risk of developing brainstem failure. Brainstem sites governing functions of the heart and of other physiological functions tend to undergo a secondary pathological change, and, causing “brain death” after a certain period time where functions of breathing and heart beating are lost. The patient's life would be irremediable when his condition passes the “irreversible point” of dying.
This condition happens generally to a patient of severe head trauma and bleeding beneath arachnoid membrane [1-2]. Clinically, IAC patient would be considered legally brain dead based on legally established standards and procedures. Inconsistencies do exists in different countries in their established standards and procedures to determine brain death, but they are based commonly on two tests, namely, the disappearance of brainstem reflexes and the apnea test [3]. The result of brainstem determination can confirm that the “irreversible point” has been reached. Nevertheless, there has been no sufficient amount of data in relative studies to accurately determine the exact point where the “irreversible point” occurs.
In Taiwan, the established standard and process for determining brain death on an IAC patient is very lengthy. When an attending physician makes a brain death determination on an IAC patient, there has to be an observation period of 12-72 hours prior to the brainstem functional test. Thereafter, the first brainstem reflexes test and an apnea test is performed to ascertain whether the patient exhibits the absence of brainstem reflexes and absolute apneal. The same two tests are repeated four hours later. The patient can be considered brain dead if the results of the repeated second set of tests confirm the absence of brainstem reflexes and absolute apnea. Due to such lengthy procedure, the patient may die halfway through the test, or before tests can be performed to determine legal brain death.
The current legal brain death determination process can not completely differentiate whether a patient has clinically reached the state of brain death. For example, because the determination of brain death needs to test whether the function of brainstem has the ability of spontaneous breathing, the precondition for an apnea test would be the normal operation of the lungs in the patient. Unfortunately, because of the absence of brainstem reflexes and already failing lung functions in many IAC patients, no apnea test can be performed on these patients. Consequently, many physicians believe this kind of IAC patients may have already achieved the state of clinical brain death.
A sympathetic storm is a hyperactive phenomenon occurring in the cardiovascular system in the event of cerebral stem infarction. In the event of cerebral stem infarction, there will be a local ischemia in cerebrospinal nerve, and in turn the sympathetic nerve can not respond to reflective stimulation, which result in tachycardia and the raise of mean arterial blood pressure, and hence into hyper-excitability [4]. In studies of organ donation patients, sympathetic storm is a common phenomenon [4-6]. Based on clinical observations, it has been found that tachycardia and hypertension can cause dramatic blood vessel constriction in IAC patients [5]. Additional studies also pointed out that studies on the heart beat variation in sympathetic storm show may have potential for facilitating the diagnosis of IAC patients [7]. So far, unfortunately, studies on sympathetic storm had been carried out merely in organ transplantation and in the laboratory. No study has yet been done applying heart beat variation in sympathetic storm on the diagnosis of clinical IAC patients.
Thus, it can be seen that the above-described brain death determination process and standard exhibits many disadvantages. It will be conducive to the established standard and procedure of determining brain death if there exists an effective analytical method specifically for IAC patients. Not only will such analytical method facilitate a physician in determining brain death of an IAC patient, it will also help in making timely arrangement of subsequent hospice care or organ donation.
Electrocardiography (ECG) had been introduced by Willem Einthoven, a Holland physiologist, to measure electric current changes during systolic phase by means of a string galvanometer, and record its changing profile on a chart. This technique was later developed into the electrocardiography (ECG) extensively used in modern medical diagnosis. The constriction of cardiac muscles is caused by a string of processes comprising polarizing, depolarizing and re-polarizing of cardiac muscles. The electric current generated during this process can distribute throughout the body such that it can be sensed by electrode patches adhered to the patient's skin. The electric current is plotted mechanically and displayed as a wave, called an electrocardiogram (ECG). Electrocardiography (ECG) depicts the initiation, order, direction, magnitude and the length of the duration of the cardiac muscle systolic current, as well as the condition of the cardiac physiological activities.
Because the frequencies of human heart beat is not very rhythmic, even at very calm and steady state, the observed interval between heart beats exhibits a variation of tens of milliseconds, which is called heart rate variability (HRV). HRV is a fluctuation that is produced from the action of cardiovascular contrition and dilation nerve center in the brain. Heart rate is influenced primarily by two factors, of which one is the constant discharge frequency of the sinoatrial pacemaker cell; the other is the control of autonomic nervous system (ANS) including sympathetic nerve system that increases heart beat and parasympathetic nerve system that suppresses heart beat [8].
Since characteristics of HRV can be changed instantly due to external environmental stimulations (e.g., postural changes, drug action, nursing activities, etc.) and intrinsic physiological mechanism (e.g., angry, happy, tension, etc.), and its length of duration of each heart beat can be affected by factors such as blood pressure change (blood pressure reflective regulation), breath (response to parasympathetic nerve from the chest pressure sensor), body temperature regulation (body temperature regulation mechanism response to the sympathetic nerve and influencing blood flow) and the circadian rhythm, long-term observation on heart beat signals can be used to monitor abnormal physiological phenomena of the heart (arrhythmia, ventricular tachycardia, ventricular fibrillation, etc.). And, therefore, HRV can be developed into a physiological monitoring index. In the electrocardiogram, the easiest measured parameter is the most significant peak-to-peak interval of R wave. Accordingly, the heart beat duration is determined generally based on the peak-to-peak interval of R wave, which is referred also as heart beat interval or R-R interval. In present researches, R-R interval is analyzed commonly with frequency domain and time domain.
The frequency domain analysis of HRV [9] is based on the fast Fourier transform (FFT) performed on R-R intervals, in which signals that are varied with time are converted into spectra of heart beat interval. A spectrum is a function of frequency; its intensity is the square of the sinusoidal amplitude of this frequency. A relative intensity can be quantified into a power spectral density (PSD). In a characteristic spectrum of a heart beat variation, two kinds of spectral peaks can be observed generally—a low frequency band and a high frequency band. There are different definitions on a low frequency band and a high frequency band in research literatures, and the most widely used definitions are low frequency in the range of 0.04˜0.15 Hz and high frequency in the range of 0.15˜0.40 Hz [9]. In the study of Akselrod et al. [9], it is pointed out that the extremely low frequency part of a spectrum governs the temperature regulation in a human body, which is within the control of sympathetic nerve, while the high frequency part manages breathing, which is within the regulation of parasympathetic nerve. The ratio between the extremely low frequency and the high frequency can be used to describe the equilibrium condition of the automatic nerve system. Further, a frequency domain marker can be utilized to measure one's psychological stress, since a psychological stress is generated from the activation of high-level cardiovascular never center and is displayed in the low frequency domain of a heart beat spectrum. The spectral analysis of a heart beat variation facilitates further identification on body temperature regulation mechanism, peripheral vessel contrition nerve, adrenaline angiotensin, and the like [9, 10].
Since the 1981 disclosure by Akselrod et al. that heart beat spectral characteristics can be used to differentiate actions between sympathetic nerve and parasympathetic nerve [9, 10], a number of different signal procession methods have been applied to resolve the interrelation between HRV and the action of automatic nerve system, as well as for assessing the action of automatic nerve system on the change of heart beat regulation under various pathological conditions [11, 12]. Instant characteristics can be utilized to monitor meanings represented by the characteristic change of heart beat induced through stimulations on the automatic nerve system under various conditions, including detecting the occurrence of local ischemia in a patient with myocardial infarction [13], evaluating the physiological condition of patients under dizziness or narcosis [14].
D'Addio et al. had analyzed the HRV of a patient with cardiac failure by means of a nonlinear analytical method, Poincaré plot, and had divided roughly the geometrical shape of a Poincaré plot into four types: comet, torpedo, fan, and complex [15, 16]. In addition, D'Addio et al. had postulated that the comet type stands for a lower heart beat and the increase of HRV; the torpedo type is narrower than the comet type and approaches a diagonal line, and represents a small difference between contiguous heart beats. In the fan type, not only is the difference between contiguous heart beats small, but contiguous heart beats as a whole is also restricted within a small range, while the complex type represents a combination of several heart beat intervals. Later, D'Addio et al. further proposed concept of 3D Poincaré plot which considered the Z axis as frequency at the same point, and presented a concept of density as well as relative parameters for 3D quantification [17]. Furthermore, Tulppo et al. [18] had proposed a way to quantify a 2D Poincaré plot, comprising an ellipsoid approach to Poincaré plot, and calculating by standard deviation the SD1 and SD2 as the major axis and minor axis, respectively, and involving parameters of SD1, SD2, SD1/SD2, and area.
Viewing that brainstem failure of a IAC patient can induce the uncontrollability of an automatic nerve, and might cause further cardiac pathological changes, the inventor believes that heart rate variability should change dramatically before and after the occurrence of a sympathetic storm in such patient, and had analyzed the heart rate variation of patients and normal peoples in order to develop an efficient IAC analytical method.